Nitrogen → 2-(6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole

HRID 880392

Reaktionsgleichung

Reaktionsgleichung von HRID 880392
Cl[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[C:4]([C:20]2[O:21][C:22]([CH2:25][N:26]3[CH2:31][CH2:30][N:29]([CH:32]([CH3:34])[CH3:33])[CH2:28][CH2:27]3)=[CH:23][N:24]=2)[CH:3]=1.CC1(C)C(C)(C)OB([C:43]2[CH:51]=[CH:50][CH:49]=[C:48]3[C:44]=2[CH:45]=[CH:46][NH:47]3)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N#N.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>CC([O-])=O.CC([O-])=O.[Pd+2].O.CC(O)C>[NH:47]1[C:48]2[C:44](=[C:43]([C:2]3[CH:10]=[C:9]4[C:5]([CH:6]=[N:7][N:8]4[S:11]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)(=[O:12])=[O:13])=[C:4]([C:20]4[O:21][C:22]([CH2:25][N:26]5[CH2:31][CH2:30][N:29]([CH:32]([CH3:33])[CH3:34])[CH2:28][CH2:27]5)=[CH:23][N:24]=4)[CH:3]=3)[CH:51]=[CH:50][CH:49]=2)[CH:45]=[CH:46]1

Komponenten

9

Edukt 5

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 113224711H-Indole-4-boronic acid, pinacol esterHCID 595647082-[1-(Benzenesulfonyl)-6-chloroindazol-4-yl]-5-[(4-propan-2-ylpiperazin-1-yl)methyl]-1,3-oxazole

Produkt 1

HCID 666957552-(6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

A mixture of 2-(6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole (1.0 eq., 1 wt, 10.0 g), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (1.1 eq., 0.535 wt, 5.35 g) and K3PO4 (1.2 eq., 0.509 wt, 5.09 g) are charged sequentially to a stirred vessel containing IPA (5 vols, 50 ml) and water (5 vols, 50 ml). KHF2 (2.2 eq., 0.344 wt, 3.44 g) is then added and the mixture heated to 75-80° C. under a flow of N2 for at least 1 hr to degas. Meanwhile, IPA (5 vols, 50 ml) is charged to a separate vessel and heated to reflux for 1 hr under a stream of N2 to degas. The IPA is cooled to 20° C. and Pd(OAc)2 (0.02 eq., 0.0090 wt, 90.0 mg) and tricyclohexylphosphine (0.04 eq., 0.0224 wt, 224 mg) are added sequentially and aged for 1 hr until a yellow solution is observed. The yellow solution is then added over 10 mins to the first vessel maintaining the temperature at 75-80° C. and stirred for at least 4 hours. The mixture is cooled to 20° C. and aged for at least 1 hr. The slurry is then filtered and washed with 1:1 IPA:water (2 vols, 20 ml) followed by water (2×2 vols, 2×20 ml) and dried in vacuo at 60±3° C. to constant temperature to afford 2-(6-(1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole as a yellow solid.

Aufarbeitung

  1. additionare charged sequentially to a stirred vessel
  2. customto degas
  3. additionMeanwhile, IPA (5 vols, 50 ml) is charged to a separate vessel
  4. temperatureheated
  5. temperatureto reflux for 1 hr under a stream of N2
  6. customto degas
  7. additionThe yellow solution is then added over 10 mins to the first vessel
  8. temperaturemaintaining the temperature at 75-80° C.
  9. temperatureThe mixture is cooled to 20° C. and aged for at least 1 hr
  10. filtrationThe slurry is then filtered
  11. washwashed with 1:1 IPA
  12. customdried in vacuo at 60±3° C. to constant temperature

Quellen und Nachweise

ORD-Eintrag
ord-edc5fcd112e24d7e82d77da7cd32eccc
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08993576B2

Verknüpfte Notizen

Wird geladen…